Synthesis of beta-D-galactosyl ceramide methylene isostere

The methylene isostere of the glycosphingolipid beta-D-galactosyl N-palmito yl C-18 ceramide has been synthesized by a linear reaction sequence startin g from a beta-linked D-galactopyranosyl aldehyde. First, this sugar aldehyd e was converted into a methylenephosphorane which in turn was coupled with N-Boc serinal acetonide. The double bond of the resulting olefin was reduce d and the oxazolidine ring was cleaved and oxidized to give a C-glycosyl N- Boc alpha-amino butanal (three-carbon chain elongation). Then, an additiona l C-15 carbon chain was installed by addition of lithium 1-pentadecyne to t he above glycosyl amino aldehyde. The syn/anti ratio (70:30) of the resulti ng mixture of amino alcohols was reversed (5:95) by an oxidation-reduction sequence to achieve the same stereochemistry as in the hydrophilic head of D-erythro-sphingosines. The major product was subjected to the reduction of the triple bond with LiAlH4 to give the olefin with E geometry. Finally th e N-amide group was installed by reaction with palmitoyl chloride and the O -benzyl protective groups of the sugar moiety were removed by treatment wit h lithium in liquid NH3-THF. The final product was characterized as the O-a cetyl derivative.